Mice expressing the Cre recombinase under control of the VE-Cadherin promoter/enhancer (VE-CAD-Cre) were purchased from Jackson Laboratory.23 (link) LKB1-floxed (LKB1flox/flox) mice were purchased from the National Cancer Institute, which was made by DePinho lab.24 (link) To generate endothelium-specific LKB1endo−/− mice, LKB1flox/flox mice were crossbred with VE-CAD-Cre mice. PCR-based genotyping was performed, as described previously.25 (link) The animals were housed in a controlled environment (20 ± 2°C, 12-h/12-h light/dark cycle), where they were maintained on a standard chow diet with free access to water. Male mice at 3 months of age were subjected to endothelial function analyses and blood pressure measurements. For adenoviral injections, wild-type (WT) or LKB1endo−/− mice received tail vein injections of 100 μL adenoviral vectors that expressed green fluorescent protein (GFP) or constitutively active (CA)-AMPK (4 × 1010 viral particles). The animal protocol was reviewed and approved by the Animal Care and Use Committee at the University of Oklahoma Health Sciences Center.